In vivo assessment of four tau protein tracers isomers of [18F]-THK5105 and [18F]-THK5117

Objectives To assess four quinoline radiopharmeuticals as potential PET biomarkers for tau pathology in Alzheimer’s disease (AD) subjects and healthy controls (HC):(R)-THK5117, (S)-THK5117, (R)-THK5105 and (S)-THK5105 isomers.

Methods 10 AD (Age 72.1, MMSE range 13-26) and 7 HC (Age 55.1) received (185 ± 3.7 MBq) of one of the four tracers and were imaged for up to 5 hours on a Siemens HR+ camera. AD subjects also underwent amyloid PET imaging. Venous blood samples were collected during imaging session to characterize metabolism of compounds. Subject's MRI was segmented for grey and white matter. PET images were co-registered onto MRI and the uptake extracted in a variety of grey matter regions. Uptake was normalized to grey matter cerebellar cortex (SUVr) and average values between 75-90 min post injection were compared between the two groups.

Results All compounds displayed very good brain penetrance with a maximum SUV of 4-6 within 10 min of injection. [18F](R)-THK5117 and [18F](S)-THK5117 had similar brain uptake kinetics that were faster than [18F](R)-THK5105 and [18F](S)-THK5105. Metabolism of all four compounds was similar with about 20-30% of intact parent remaining at 90 min post injection. SUVr for [18F](R)-THK5117, [18F](S)-THK5117, and [18F](S)-THK5105 were increased in AD compared to HC in regions expected to demonstrate tau pathology, with increase of 30-40% in the inferior lateral temporal cortex.

Conclusions These preliminary data suggest that both [18F](R)-THK5117 and [18F](S)-THK5117 appear to detect tau pathology in AD subjects. The kinetic profile and tracer performance of [18F](R)-THK5117 and [18F](S)-THK5117 seem superior than of [18F](R)-THK5105 and [18F](S)-THK5105 to image tau protein in human brain. Further studies are ongoing to characterize the binding of these tracers in AD and related neurodegenerative disorders.